Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption

Area of Science:

• Neuroscience
• Neurobiology
• Pharmacology

Background:

• Compulsive alcohol drinking is a hallmark of alcohol use disorder (AUD) and is highly resistant to treatment.
• Perineuronal nets (PNNs) in the insular cortex modulate aversion-resistant drinking in male mice.
• Female mice exhibit higher aversion-resistant ethanol intake, but the role of PNNs in this behavior remains unexamined.

Purpose of the Study:

• To compare PNNs in the insula of male and female mice.
• To investigate if disrupting PNNs in female mice alters aversion-resistant ethanol intake.
• To explore sex differences in the neural mechanisms underlying aversion-resistant alcohol consumption.

Main Methods:

• PNNs in the insula were visualized using Wisteria floribunda agglutinin (WFA) fluorescent labeling.
• PNNs were disrupted in female mice via microinjection of chondroitinase ABC.
• Aversion-resistant ethanol consumption was assessed using a two-bottle choice drinking in the dark procedure with quinine.
• Insula activation was measured using c-fos immunohistochemistry.

Main Results:

• PNN staining intensity was greater in the insula of female mice compared to male mice.
• Disruption of PNNs in female mice had a limited effect on aversion-resistant ethanol intake.
• Insula activation during aversion-resistant drinking was lower in female mice than in male mice.

Conclusions:

• Neural mechanisms underlying aversion-resistant ethanol consumption appear to differ between male and female mice.
• PNNs in the female insula may not be the primary driver of elevated aversion-resistant drinking.
• Further research is needed to elucidate the sex-specific neurobiology of AUD.